This program project has developed from the long standing interest of an active and interactive group of investigators at the NYU Medical Center in cell surface molecules of relevance to the immune system. The participants bring together a wide variety of interests and technical skills, ranging from somatic cell genetics to classic protein chemistry and includes molecular genetics, DNA-mediated gene transfer and serology with conventional and monoclonal antibodies. The group has collaborated as the Molecular Immunology Unit of the Cancer Center for 5 years and is part of the larger immunology group at NYU which has met together on a weekly basis for the past 25 years. The project focuses on the differentiation antigens expressed by the cells of the immune system. Five projects are proposed: 1) The function of complement receptor 2 (CR2); 2) Isolation and structure of a human macrophage marker gene; 3) Cloning of minor H genes; 4) Studies of the role of T-cell differentiation antigens in the expression of effector functions in cloned prothymocyte cell lines; and 5) lymphocyte heterodimer expression: Do chromosomes converse? Membrane components characteristic of B-cells, T-cells and macrophages are under study and particular attention is being devoted to the mechanisms that control their expression. To understand the role of each of the components of the immune system, it will ultimately be necessary to identify and characterize the molecules produced by these cells which mediate their specific function. Many of these molecules are likely to be expressed at the cell surface, where they interact with the environment, serving either effector or recognition functions. Their expression is highly regulated in terms of developmental sequence and coordinated in that the products of several genes are required simultaneously at each step in the process.